QSAR analysis of the toxicity of nitroaromatics in Tetrahymena pyriformis : structural factors and possible modes of action

The Hierarchical Technology for Quantitative Structure - Activity Relationships (HiT QSAR) was applied to 95 diverse nitroaromatic compounds (including some widely known explosives) tested for their toxicity (50% inhibition growth concentration, IGC50) against the ciliate Tetrahymena pyriformis. The dataset was divided into subsets according to putative mechanisms of toxicity. Classification and Regression Trees (CART) approach implemented within HiT QSAR has been used for prediction of mechanism of toxicity for new compounds. The resulting models were shown to have ~80% accuracy for external datasets indicating that the mechanistic dataset division was sensible. Then, Partial Least Squares (PLS) statistical approach was used for the development of 2D QSAR models. Validated PLS models were explored to (i) elucidate the effects of different substituents in nitroaromatic compounds on toxicity; (ii) differentiate compounds by probable mechanisms of toxicity based on their structural descriptors; (iii) analyze the role of various physical-chemical factors responsible for compounds’ toxicity. Models were interpreted in terms of molecular fragments promoting or interfering with toxicity. It was also shown that mutual influence of substituents in benzene ring plays the determining role in toxicity variation. Although chemical mechanism based models were statistically significant and externally predictive (R2ext=0.64 for the external set of 63 nitroaromatics identified after all calculations have been completed), they were also shown to have limited coverage (57% for modeling and 76% for external set)

Relationship Between the H5 Chondrite Composition, Structure and Mechanical Properties from the Example of NWA 12370 and Pultusk

Abstract—: The peculiarities of the composition and internal structure of chondrite NWA 12370, petrological type H5 S1 W1, were studied by means of Raman spectroscopy, XRF, and electronic sounding. The dependence of the mechanical properties of chondrite on the external hydrostatic pressure was studied by means of ultrasonic waves and static methods. This meteorite is a fragment of stone rain from the debris of the inner part of a large asteroid, about 200 km in size. We compared the mechanical characteristics obtained with those of the well-studied Pultusk chondrite of the same type, impact breccia H4/H5 S2 W1. At the early stage of the Solar System, such planetesimals made a significant contribution to the geochemical evolution of the terrestrial planets. Therefore, understanding the peculiarities of the relationship between the H chondrite’s internal structure and elastic properties is essential for assessing their contribution to the crust and upper mantle composition of the Earth and Moon and clarifying the conditions for the formation of the redox potential of the planetary interior

ЭПИДЕМИОЛОГИЯ ПЕРВИЧНОГО ЭНДОПРОТЕЗИРОВАНИЯ ТАЗОБЕДРЕННОГО СУСТАВА НА ОСНОВАНИИ ДАННЫХ РЕГИСТРА АРТРОПЛАСТИКИ РНИИТО ИМ. Р.Р. ВРЕДЕНА

The   paper   presents   data   analysis   of  the   Hip   Arthroplasty  Register   of  Vreden   Russian   Research   Institute of Traumatology and Orthopedics, namely information on 37373 primary THA performed at the Vreden Institute and at several other orthopedic centers and 1200 hip replacements at other hospitals of St. Petersburg.There were 1.5 times more women in the studied cohort than men. A significant predominance of women with dysplastic osteoarthritis (72.4%) and rheumatoid arthritis (82.1%) was reported. A male predominance was noted in patients with secondary osteoarthritis (53.1%), post-traumatic changes of hip (61.0%) and osteonecrosis of the femoral head (68.6 %). The mean age of patients was 58.0±12.9 years (95% CI from 57.9 to 58.1, median 59 years). Age data of the study revealed that  patients were 10-12 years younger than reported in the national  arthroplasty registers of other countries.Total  hip arthroplasty was performed  in the  absolute  majority  of patients – 37295  cases (99,8%).  Uncemented implants  were used in 59.3% of cases, hybrid – in 29.6%, cemented – in 10.2%, reverse-hybrid – in 0.9% of all patients. The  most  common  bearing  used  was metal  on  crosslink  polyethylene, which  was applied  in 50.1% of all cases of arthroplasty. The  type  of fixation  of the  implant,  and  the  use of different  bearings  varied  in different  age groups. The paper presents  not only the absolute  numbers  of the data, but also demonstrated the dynamics  of the changes in time starting from 2007.The  present  epidemiological  study  does not  claim the  absolute  completeness of the  presented data,  but  contains the  analysis of the  large number  of cases, comparable  with  follow-ups  of patients in some national  registers  of certain European countries. The authors  analyzed about  10% of all cases of hip replacements performed  on the territory of the Russian Federation in ten-year  period.Представлен анализ  данных  регистра  эндопротезирования  тазобедренного сустава  (ТБС)  РНИИТО  им. Р.Р.  Вредена,  в котором  содержатся  сведения  о 37 373 операциях,  выполненных в институте  и ряде  федеральных  центров,  и 1200  случаях  эндопротезирования тазобедренного сустава,  выполненных в других  больницах Санкт-Петербурга.В исследуемой когорте пациентов женщин было в 1,5 раза больше, чем мужчин. Отмечается значительное преобладание  женщин  при диспластическом коксартрозе (72,4%)  и ревматоидном артрите  (82,1%).  Преобладание мужчин  отмечалось  в группе  пациентов  с вторичными артрозами  (53,1%),  посттравматическими изменениями ТБС (61,0%) и АНГБК  (68,6%). Средний возраст пациентов составил 58,0±12,9 лет (95% ДИ от 57,9 до 58,1, медиана 59 лет). эти возрастные  показатели на 10–12 лет ниже, чем в национальных регистрах артропластики других стран.Абсолютному большинству пациентов выполнялось тотальное эндопротезирование ТБС – 37295 наблюдений (99,8%). Бесцементная фиксация компонентов эндопротезов  использовалась в 59,3% случаев, гибридная в 29,6%, цементная  в 10,2%, реверс-гибридная – в 0,9% всех наблюдений.  Самой  распространенной парой  трения  была металл-кросслинк полиэтилен, которая использовалась в 50,1% всех случаев эндопротезирования. Тип фиксации эндопротеза  и применение той или иной пары трения различаются в разных возрастных  группах. В статье приведены не только абсолютные  цифры этих показателей, но и показана динамика их изменений во времени, начиная с 2007 г.Данное эпидемиологическое исследование не претендует  на абсолютную  полноту  представленных сведений, но является анализом  очень большого числа случаев, сопоставимых по объему наблюдений  с некоторыми национальными регистрами небольших европейских стран. В целом в работе анализируется около 10% всех операций по замене ТБС, выполненных на территории Российской Федерации в десятилетний период